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THE LANCET

Two for the Price of One ?

IN his message to Congress, President Nixorr

proposed, as a major objective for American science,a$300 million programme to produce a cure forcancer. Taken at its face value, this step seems toput behind the slogan of the Imperial Cancer ResearchFund (Conquer Cancer in the ’70s) the same kind ofbacking which was given by earlier incumbents ofthe White House to the Manhattan Project and themoon landing. The difference in investment couldbe due simply to the fact that biological research isimmeasurably cheaper than projects requiring expen-sive hardware. A part of the programme is likely tobe environmental, but by far the largest emphasiswill be on new research.What are the chances of success for a crash pro-

gramme ? On all the evidence, the prospects lookreasonably good. Overoptimism is probably not afailing of the President’s science forecasters: " cures "for cancer, or at least a one-shot theory of causation,have seemed to be within our grasp before but haveremained cruelly out of reach. The Gordon-HelmerDelphi study 1,2 put the median date for an effectivecancer chemotherapy around 1990. Experience hasshown that technology forecasts of this type tend tooverrate the 5-10-year prospects and to underratethe 15-20-year prospects. The point of a crashprogramme is that quick results, though not certain,must be possible to a degree which makes it worthattempting them. Apart from single therapeuticagents such as I-asparaginase, from which clinicaland theoretical " spinoff " is not yet complete, andfrom ongoing studies which are already heavily fun-ded, such as that on the nature of C particles,3 threemain fields could easily yield a crop which would beat worst instructive and at best clinically applicablewithin 5-10 years-immunology, molecular biology,including virology, and the study of transformationin clones. The first may well offer the best approachto the prevention and control of malignancy in thelong to medium term, by way of an understandingof the body’s immunosurveillance mechanism. Thesecond has already turned up the potentially im-portant discovery of reverse transcriptases whichcopy R.N.A. into D.N.A.,4 while the third is engaged1. Gordon, T. J., Helmer, O. Rand Corporation Publication p-2982.

Santa Barbara, California, 1964.2. Subcommittee on Science, Research and Development, Nov. 18, 24;

Dec. 2, 3, 4, 8, 12, 1969. U.S. Government Printing Office.3. Bazell, R. J. Science, 1970, 170, 304.4. Nature, 1970, 228, 410; see Lancet, 1970, ii, 1349.

in uncovering the surface differences between trans-formed, malignant clones, insusceptible to contact

inhibition, and " normal " somatic cells.5 Any oneof these areas, or all three in convergence, would bewell worth backing for a place. Such an approachwould be a great improvement on mass screening ofchemicals at random, often by unsuitable tests, for" anti-tumour " activity.The main question about the President’s initiative

is whether, by a slight broadening of its scope, itsimportance for medicine and the human conditionmight not be enormously increased: whether, inother words, an exclusive concentration on cancer,rather than on the life-cycle of which it is part, maynot represent a loss of still bigger game, scientificand psychological. The Gordon-Helmer survey alsopredicted a major increase in lifespan through thecontrol of the rate of ageing by the year 2023. Allow-ing for the time taken for longevity studies in man toprove themselves, this puts the two projects in

tandem, and it is not without importance that all thethree disciplines which look most likely to profitcancer research-immunology, molecular biology in-cluding

" error theory ", and the nature of mortality

in clones-are deeply involved in attempts to eluci-date the nature of the information loss with age. In

fact, the total cure of all cancers, while removing acloud from the horizon of the older American, andending the tragedy of cancer in the young or themiddle-aged, will add only about 1.5 years to the

expectation of life at 65: older Americans will diealmost as soon of something else, chiefly degenerativedisease.

Cancer, in fact, whether its origins be viral,mutational, or other, is almost certainly a specialcase of the wider process of mis-specification whichappears to be involved in our deterioration with age.It might just be possible to control cancers withoutcontrolling ageing: it would not be possible to controlageing without controlling cancer. The philosophybehind an extension of the cancer effort is that both

ageing and liability to tumours seem to be post-ponable in animals by the same, reasonably simple,means; that should current threads leading to thecancer prize prove longer than expected, postpone-ment of age changes would at least put off tumoursthat cannot be prevented or cured; and that, bio-logically speaking, it ought to be far easier to alter arate than to rewrite a programme. In fact, most ofthe experiments and facilities needed for one project- a test-battery to measure ageing-rate,6 for example- are also needed for the other. By widening theunderlying objective, America could have two

renowned and humane achievements for the

price of one: without some control of the de-

generations-which, though less feared, are in many

5. Nature, 1970, 228, 502; see Lancet, 1970, ii, 1294.6. Comfort, A. Lancet, 1969, ii, 1411.

328

ways crueller destroyers of the quality of life thanare the malignancies-the victory over cancer couldbe a hollow one, transferring yet another burden toalready overloaded palliative services in old age.There is, in fact, already a means to hand by

which this enormously productive broadening of ob-jective could be achieved. A White House conferenceis about to convene to discuss the problems of

ageing, chiefly in the socioeconomic context: there isalso a draft measure, sponsored by Senator WILLIAMS,of New Jersey, and an influential group of scientists,to set up a National Aging Commission on thelines of N.A.S.A., aimed to mount a specific andproject-oriented attack on the nature of human

ageing. Whether or not the details of the WilliamsBill appeal to the President, it would be easy for himto extend the rubric of his cancer proposal on hisown terms, to increase all the gains-medical,scientific, and political-which his initiative could

yield.

Where Do They Come From ?INFLUENZA viruses are about 80-120 mµ, in diameter

and consist of an internal ribonucleoprotein (R.N.P.)component surrounded by a spiky outer envelope. 1,2All influenza-A viruses, whether they cause infectionin man, pigs (swine influenza), horses, or chickens(fowl plague), share a common stable R.N.P. antigen,which is distinct from the R.N.P. antigen of influenzaB, which in turn differs from that in influenza C.Neither influenza B nor C has so far been isolatedfrom lower animals under natural conditions. Theouter envelope is also antigenic, and changes in thispart of the virus are responsible for producing anti-genic variations, both major and minor.

Influenza-A virus was first isolated in London

during the 1932-33 epidemic.3 This virus continuedto cause epidemics of varying severity up to 1946,after which it was replaced by a new antigenic type,which in turn was replaced by yet a further anti-genically dissimilar influenza-A virus which causedthe 1957 pandemic of Asian influenza. These threemain serotypes are designated AO, Al, and A2respectively. In addition to these major changes,minor degrees of antigenic " drift " occur, such asthe emergence in 1968 of the Hong Kong strainof A2, which caused the severe epidemic of influenzain the United Kingdom during the winter of 1969-70.Serological studies employing hxmagglutination-inhibition tests on sera collected from groups ofindividuals of different age-groups strongly suggestthat the 1957 A2 virus was closely related to the virus1. Home, R. W., Waterson, A. P., Wildy, P., Farnham, A. E. Virology,

1960, 11, 79.2. Waterson, A. P., Hurrell, J. M. W., Jensen, K. E. Arch. ges. Virus-

forsch. 1962, 12, 487.3. Smith, W., Andrewes, C. H., Laidlaw, P. P. Lancet, 1933, ii, 66.

which caused the pandemic of 1889-90 4,5; and laterresults indicated that the 1968 Hong Kong derivativemay have been similar to a virus which circulated atthe turn of the century, having succeeded the 1889-90prototype. It has also been shown that the A2/HongKong/68 virus is antigenically related to a horseinfluenza virus, A/equi/2/63,7 and people who werealive at the turn of the century but whose sera werecollected before the advent of the A2/Hong Kong/68epidemic contained antibody to this virus. 6 This

equine virus is capable of infecting man experiment-ally. 8 These findings lend further support to

FRANCIS’S hypothesis that the emergence of " new "strains of influenza-A virus follows a cyclical course.9But from where do these " new " strains arise ?

The role of animals as possible reservoirs of infectionhas been much debated, ever since retrospectiveserological studies suggested that the virus of classicalswine influenza, which first caused epidemics of acuterespiratory infection amongst pigs in the mid-Western States of the U.S.A. during the 1918 pan-demic, was closely related to the virus which alsocaused human infection at that time.10,11 The viruswas probably transmitted to pigs from humans. Inaddition to the antigenic relationships existingbetween human, swine, and equine viruses, antigenicrelationship has also been detected between humanand avian influenza viruses.12 However, the develop-ment of techniques to isolate viral surface antigensand to measure antibody directed against themseparately has resulted in the recognition of not onebut two distinct virus-coded protein units-the

hsemagglutinin and an enzyme, neuraminidase. This

enzyme is probably concerned in the release of

progeny influenza virus from infected cells. Tech-

niques which assay both hæmagglutinin and neur-aminidase have led to a clearer understanding of theantigenic relationship between influenza viruses ofman and lower animals as well as the mechanism bywhich antigenic drift may occur. Thus, althoughA2/Hong Kong/68 virus has a hxmagglutinin whichdiffers strikingly from previous influenza-A2 strains,it shares an antigenically related neuraminidase withthem. 13 3 If the neuraminidase had also changed in1968, the emergent virus would have been influenzaA3 rather than A2/Hong Kong!68. AlthoughA2/Hong Kong/68 and A/equi/2/63 have closelyrelated haemagglutinins, their neuraminidases are

4. Mulder, J., Masurel, N. ibid. 1958, i, 810.5. Clarke, S. K. R., Heath, R. B., Sutton, R. N., Stuart-Harris, C. H.

ibid. p. 814.6. Masurel, N. ibid. 1969, i, 907.7. Kasel, J. A., Fulk, R. V., Couch, R. B. J. Immunol. 1969, 102, 530.8. Alford, R. H., Kasel, J. A., Lehrich, J. R., Knight, V. Am. J.

Epidem. 1967, 86, 185.9. Francis, T. Proc. Am. phil. Soc. 1960, 104, 572.

10. Shope, R. E. J. exp. Med. 1936, 63, 669.11. Davenport, F. M., Hennesy, A. V., Francis, T., Jr. ibid. 1953, 98,

641.12. Pereira, H. G., Tumova, B., Webster, R. G. Nature, 1967, 215, 982.13. Schulman, J. L., Kilbourne, E. D. Proc. natn. Acad. Sci. U.S.A.

1969, 63, 326.